Edelweiss Aldasoro

Prevalence of Chagas disease in Latin-American migrants living in Europe: a systematic review and meta-analysis.

Background Few studies have assessed the burden of Chagas disease in non-endemic countries and most of them are based on prevalence estimates from Latin American (LA) countries that likely differ from the prevalence in migrants living in Europe. The aim of this study was to systematically review the existing data informing current understanding of the prevalence of Chagas disease in LA migrants living in European countries. Methods We conducted a systematic review and meta-analysis of studies reporting prevalence of Chagas disease in European countries belonging to the European Union (EU) before 2004 in accordance with the MOOSE guidelines and based on the database sources MEDLINE and Global Health. No restrictions were placed on study date, study design or language of publication. The pooled prevalence was estimated using random effect models based on DerSimonian & Laird method. Results We identified 18 studies conducted in five European countries. The random effect pooled prevalence was 4.2% (95%CI:2.2-6.7%); and the heterogeneity of Chagas disease prevalence among studies was high (I2 = 97%,p<0.001). Migrants from Bolivia had the highest prevalence of Chagas disease (18.1%, 95%CI:13.9–22.7%). Conclusions Prevalence of Chagas in LA migrants living in Europe is high, particularly in migrants from Bolivia and Paraguay. Data are highly heterogeneous dependent upon country of origin and within studies of migrants from the same country of origin. Country-specific prevalence differs from the estimates available from LA countries. Our meta-analysis provides prevalence estimates of Chagas disease that should be used to estimate the burden of disease in European countries.

Immunosuppression and Chagas disease: a management challenge.

Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally incorporated into management protocols for immunosuppressed patients. International consensus guidelines based on expert opinion would greatly contribute to standardizing the management of immunosuppressed patients with Chagas disease.

Therapeutic plasma exchange for the management of refractory systemic autoimmune diseases: report of 31 cases and review of the literature.

INTRODUCTION Therapeutic plasma exchange (TPE) represents a treatment option in patients with systemic autoimmune diseases because most of their clinical manifestations are related to the presence of antibodies or immune complex deposition. OBJECTIVE To describe the main demographic and clinical characteristics as well as the outcome of patients with systemic autoimmune diseases treated with TPE at a tertiary care center. METHODS We included all patients with systemic autoimmune diseases in whom the indication for treatment with TPE was a flare of the disease between 1999 and 2010. The indications for treatment, complications and outcomes were obtained from review of medical records. RESULTS A total of 31 patients (18 (58%) females and 13 (42%) males) were treated with a total of 196 TPE sessions with an average of 6.3 sessions per patient. Mean age at the time of TPE was 52.9 years (range, 26.0-82.0 years). Ten (32.3%) patients had ANCA-associated vasculitides, 6 (19.4%) mixed cryoglobulinemia secondary to hepatitis C virus (HCV) infection, 5 (16.1%) essential mixed cryoglobulinemia, 4 (12.9%) catastrophic antiphospholipid syndrome, 3 (9.7%) systemic lupus erythematosus, 2(6.5%) dermatomyositis and 1 (3.1%) polyarteritis nodosa. All patients except one were receiving corticosteroids at varying doses and all received a concomitant immunosuppressive drug. Ten (32.3%) and 9 (29.0%) patients received rituximab and intravenous immunoglobulins prior to TPE, respectively. Six patients experienced catheter-related infections, 5 urinary infections and 3 patients developed hospital acquired pneumonia. Eleven patients died in spite of the TPE. CONCLUSIONS TPE is an effective therapeutic option for treating serious manifestations of systemic autoimmune diseases and a valid option for those patients with refractory disease to conventional treatments.

Population pharmacokinetics of benznidazole in adult patients with Chagas disease

ABSTRACT The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/F) and the apparent volume of distribution (V/F), with first-order absorption (Ka) and elimination, adequately described the data (CL/F, 1.73 liters/h; V/F, 89.6 liters; and Ka, 1.15 h−1). No covariates were found to be significant for CL/F and V/F. Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011-002900-34 and at ClinicalTrials.gov under number NCT01755403.)

Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014.

Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic. The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.

Refractory giardiasis in Spanish travellers.

Drug failure is a common cause of symptom persistence after treatment of imported Giardia duodenalis. In this retrospective study we describe a high prevalence of refractory giardiasis in people attended in a travel clinic in Spain, especially those with infections acquired in Asia. Moreover, we discuss various treatment strategies to tackle G. duodenalis that is refractory to nitroimidazoles.

Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis

BACKGROUND Chagas disease is currently prevalent in European countries hosting large communities from Latin America. Whether asymptomatic individuals at risk of Chagas disease living in Europe should be screened and treated accordingly is unclear. We performed an economic evaluation of systematic Chagas disease screening of the Latin American population attending primary care centres in Europe. METHODS We constructed a decision tree model that compared the test option (screening of asymptomatic individuals, treatment, and follow-up of positive cases) with the no-test option (screening, treating, and follow-up of symptomatic individuals). The decision tree included a Markov model with five states, related to the chronic stage of the disease: indeterminate, cardiomyopathy, gastrointestinal, response to treatment, and death. The model started with a target population of 100 000 individuals, of which 4·2% (95% CI 2·2-6·8) were estimated to be infected by Trypanosoma cruzi. The primary outcome was the incremental cost-effectiveness ratio (ICER) between test and no-test options. Deterministic and probabilistic analyses (Monte Carlo simulations) were performed. FINDINGS In the deterministic analysis, total costs referred to 100 000 individuals in the test and no-test option were €30 903 406 and €6 597 403 respectively, with a difference of €24 306 003. The respective number of quality-adjusted life-years (QALYs) gained in the test and no-test option were 61 820·82 and 57 354·42. The ICER was €5442. In the probabilistic analysis, total costs for the test and no-test option were €32 163 649 (95% CI 31 263 705-33 063 593) and €6 904 764 (6 703 258-7 106 270), respectively. The respective number of QALYs gained was 64 634·35 (95% CI 62 809·6-66 459·1) and 59 875·73 (58 191·18-61 560·28). The difference in QALYs gained between the test and no test options was 4758·62 (95% CI 4618·42-4898·82). The incremental cost-effectiveness ratio (ICER) was €6840·75 (95% CI 2545-2759) per QALY gained for a treatment efficacy of 20% and €4243 per QALY gained for treatment efficacy of 50%. Even with a reduction in Chagas disease prevalence to 0·05% and with large variations in all the parameters, the test option would still be more cost-effective than the no-test option (less than €30000 per QALY). INTERPRETATION Screening for Chagas disease in asymptomatic Latin American adults living in Europe is a cost-effective strategy. Findings of our model provide an important element to support the implementation of T cruzi screening programmes at primary health centres in European countries hosting Latin American migrants. FUNDING European Commission 7th Framework Program.

Genotypic Characterization of Enterotoxigenic Escherichia coli Strains Causing Traveler's Diarrhea

ABSTRACT This study aims to characterize the presence of virulence factors of enterotoxigenic Escherichia coli (ETEC) causing travelers diarrhea. Among 52 ETEC isolates, the most common toxin type was STh, and the most frequent colonization factors (CFs) were CS21, CS6, and CS3. On the other hand, the nonclassical virulence factors EAST1 and EatA were frequently present.

Evaluation of a chemiluminescent enzyme-linked immunosorbent assay for the diagnosis of Trypanosoma cruzi infection in a nonendemic setting

The disappearance of lytic, protective antibodies (Abs) from the serum of patients with Chagas disease is accepted as a reliable indicator of parasitological cure. The efficiency of a chemiluminescent enzyme-linked immunosorbent assay based on a purified, trypomastigote-derived glycosylphosphatidylinositol-anchored mucin antigen for the serologic detection of lytic Abs against Trypanosoma cruzi was evaluated in a nonendemic setting using a panel of 92 positive and 58 negative human sera. The technique proved to be highly sensitive {100%; 95% confidence interval (CI) = 96-100} and specific (98.3%; 95% CI = 90.7-99.7), with a kappa score of 0.99. Therefore, this assay can be used to detect active T. cruzi infection and to monitor trypanosomicidal treatment.

Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response

Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole.